Easy Access to Functionalized Indolines and Tetrahydroquinolines via a Photochemical Cascade Cyclization Reaction.

Herein, the development of a light-mediated synthesis of functionalized indolines and tetrahydroquinolines is reported. These structural motifs are considered as highly valuable targets, attributed to their widespread occurrence in pharmaceuticals and natural products. The gold-mediated approach offers a direct route to functionalized indolines in yields of up to 81% under mild photochemical conditions. Thereby, easily accessible Boc-protected N-aryl-allylamine and homoallylamine derivatives were reacted with sp3-hybridized haloalkanes in an intermolecular cascade cyclization reaction. A broad scope of substrates, including a variety of different substituents on the aromatic backbone as well as various haloalkanes, could be utilized. Indoline derivatives, which are functionalized in position 2, are also accessible by applying ortho-allylic anilines. Moreover, the synthetic appeal was demonstrated for a total synthesis of the anti-inflammatory agent AN669 in three reaction steps in an overall yield of 64%.

Gold Meets Selenium: Dual Activation of Selenium-Containing Propargyl Alcohols Towards the Synthesis of 2H-Chromenes and Mechanistic Insights.

Herein, we report the synthesis of seleno-substituted chromenes from selenoalkynes and phenols. In this cascade reaction, the applied gold catalyst not only functions as a p-acid, but also as a Lewis acid, enabling the propargylic substitution in the first step to connect the oxygen carbon bond. Under the optimal reaction condition a total of 26 chromenes were accessible by this modular access. During scale up experiments, the hydrolysis of the vinylselenium substructure to the corresponding chromenones was observed. By revisiting the electron-rich starting materials, four chromenones were produced following a one-pot reaction using a single gold catalyst. To better understand the interaction of gold and selenium, a series of nuclear magnetic resonance studies and high-resolution mass spectrometry studies were performed, which led to the proposal of a mechanism for this transformation.

Mn(III) O

Polyurethanes are synthesized on industrial scale by the reaction of diisocyanates with diols in the presence of catalysts which are commonly based on tin complexes and amines. However, due to the toxicity and volatility of these tin catalysts and amines, there is the need to develop new catalysts that are more environmentally benign. Herein, we report the synthesis of O^N^O pincer-ligated Mn(III) and Fe(III) complexes that serve as suitable catalysts for urethane formation and are stable to hydrolysis as predicted by computations and observed experimentally. The O^N^O pincer scaffold is vital to the activity of these catalysts, simultaneously ensuring increased solubility in the reaction medium as well as providing a stable framework upon dissociation of co-ligands in the catalytic cycle. In silico mechanistic investigations for urethane formation show that the stabilization of active species in square-planar geometries enabled by these O^N^O ligands permit the simultaneous coordination of alcohol and isocyanate in suitable configuration at the metal center.

Copper(II)-Catalyzed Amination of Aryl Chlorides in Aqueous Ammonia.

Anilines are ubiquitous in bio-active compounds and their synthesis can be achieved via metal-catalyzed cross-coupling reactions involving aryl halides. We describe an unusual, yet simple, CuII-catalyzed system for the amination of aryl chlorides in pure aqueous ammonia with 2.5 mol% catalyst loading under non-inert conditions. Different from previous systems, the reaction proceeds even without an additional organic solvent. Copper(II) sulfate in combination with 4,7-dimethoxy-1,10-phenanthroline enabled the amination of several aryl chlorides containing electron-neutral, -donating and -withdrawing groups to the corresponding anilines with good to excellent yields. The upscaling potential of the procedure has been shown by the synthesis at 50 mmol scale. The reaction proceeds as one of the rare cases of a CuII-assisted coupling, in contrast to the typical CuI-CuIII intermediates postulated for most Ullmann-type coupling reactions. The copper(II) center allows for a nucleophilic substitution pathway, enabled by the deprotonation of coordinated ammonia.

Title Selective Coupling of ß-(Borylvinyl)silanes by a Gold-catalyzed Hiyama Reaction - An Easy Way to Diaryl-Substituted Vinyl Boronates.

Diaryl-substituted vinyl boronates as potent building modules are challenging to synthesize. Herein, we present a convenient strategy based on a gold-catalyzed Hiyama arylation of (Z)-ß-(borylvinyl)silanes which are easily accessible by hydroboration of silylalkynes. By exploiting the highly electronegative nature of the Au(III) intermediate (which is accessed by the light-assisted oxidation with aryl diazonium salts), a selective activation of the silyl group in the presence of the boron moiety is achieved. This opens a route to selectively synthesize diaryl-substituted vinyl boronates. The reaction shows a broad substrate range, excellent functional group tolerance and perfect chemo-selectivity. Experimental studies and DFT calculations allowed us to elucidate the mechanism of the reaction, the synthetic potential was demonstrated by downstream transformations providing a facile route to bifunctional phenanthrenes and triaryl-substituted olefins.

Cascade Reactions of Aryl-Substituted Terminal Alkynes Involving in Situ-Generated α-Imino Gold Carbenes.

An efficient, highly selective and divergent synthetic method to construct 2-substituted indoles and aryl-annulated carbazoles via the intermolecular generation of α-imino gold carbenes from terminal alkynes or diynes in combination with sulfilimines is disclosed. Importantly, the tandem reaction is proposed to proceed through an intermolecular gold carbene generation/C-H annulation followed by the activation of a second alkyne leading to 6-endo-dig cyclization, which is significantly different from previous dual activation or 1,6-carbene shift approaches for diyne systems. In the case of ortho-alkynylaniline as starting material, an unexpected regioselective formation of the indole moiety via the intermolecular path, instead of intramolecular hydroamination was discovered. This reactivity paved the way for a one-pot synthesis of the 11H-indolo [3,2-c] quinoline scaffold by exploiting the formed amino indole for a subsequent Pictet-Spengler reaction with aldehydes. The photophysical properties of the carbazoles indicated good violet-blue emission with quantum yields up to 40 %.

Gold(I)-Catalyzed Intramolecular 7-endo-dig Cyclization of Triene-Yne Systems: New Access towards Azulenothiophenes.

We report the direct synthesis of new azulene derivatives through gold-catalyzed cyclization reactions. A five-membered ring as backbone in the applied triene-yne substrates turned out to be crucial to induce the 7-endo-dig cyclization mode necessary to trigger azulene formation. The obtained targets are of high interest due to their potential applications in different fields, like organic materials, medicine or cosmetics. UV/Vis spectra and cyclic voltammetry were measured, based on these the electronic properties were determined. Short two or three step sequences towards the applied starting materials make this approach synthetically highly attractive.

Gold(I)-Mediated Cyclizations of Triene-Yne Systems: An Easy Access to Cyclopenta-Fused Anthracenes.

The direct synthesis of cyclopenta-fused anthracenes (CP-anthracenes) through a gold(I)-catalyzed cyclization reaction of easily available triene-yne systems bearing a benzofulvene substructure, is reported. The targets are of great interest due to the potential use as organic materials and the preparation of these compounds is gaining huge importance. The applied starting materials are readily available through a three-step synthesis, which further contributes to the advantages of this route. In addition, UV-Vis and fluorescent spectra of the obtained CP-anthracenes were recorded.

Gold-Catalyzed Regio- and Stereoselective α-Acyloxy-ß-Alkynylation of Ynol Ethers.

Enol esters and conjugated enynes are valuable structural motifs for synthetic chemistry and material sciences. Herein, the synthesis of tetra-substituted enol ester 2-iodobenzoate derivatives was achieved in good yields at room temperature through a gold-catalyzed acyloxyalkynylation of sensitive ynol ethers with ethynylbenziodoxolones (EBXs), the latter acting as bifunctional reactants. The conversion is highly regioselective with a broad substrate scope. Mechanistically, an Au(III) species is the key intermediate of an Au(I)/Au(III) redox cycle. The reaction is synthetically useful and can easily be scaled up to gram scale.

1,2-Migrations onto Gold Carbene Centers.

Gold carbenes are highly active intermediates in homogeneous gold catalysis, enabling a large array of transformations such as C-H/X-H insertions, cyclopropanations, and 1,2-migrations. Unlike C-H/X-H insertions and cyclopropanations, 1,2-migrations onto gold carbene centers seem to be attracting less attention. There has been no comprehensive review focusing on this topic, even though this chemistry has become a powerful tool for the rapid and simple construction of molecular complexity. This review provides comprehensive and critical information on the 1,2-migrations onto gold carbene centers, drawing a preliminary conclusion on the migratory aptitude of various groups. The review is divided into several parts according to the kind of carbene precursors.

Light in Gold Catalysis.

Within the wide family of gold-catalyzed reactions, gold photocatalysis intrinsically features unique elementary steps. When gold catalysis meets photocatalysis, a valence change of the gold center can easily be achieved via electron transfer and radical addition, avoiding the use of stoichiometric sacrificial external oxidants. The excellent compatibility of radicals with gold catalysts opens the door to a series of important organic transformations, including redox-neutral C-C and C-X coupling, C-H activation, and formal radical-radical cross-coupling. The photocatalysis with gold complexes nicely complements the existing photoredox catalysis strategies and also opens a new avenue for gold chemistry. This review covers the achieved transformations for both mononuclear gold(I) catalysts (with and without a photosensitizer) and dinuclear gold(I) photocatalysts. Various fascinating methodologies, their value for organic chemists, and the current mechanistic understanding are discussed. The most recent examples also demonstrate the feasibility of both, mononuclear and dinuclear gold(I) complexes to participate in excited state energy transfer (EnT), rather than electron transfer. The rare applications of gold(III) photocatalysts, both homogeneous and heterogeneous, are also summarized.

Homogeneous and Heterogeneous Gold Catalysis for Materials Science.

Often stoichiometric amounts of gold find use in materials science; occasionally gold is even used as a support. This review discusses the contributions of gold catalysis, both homogeneous and heterogeneous, to the field of materials science. One topic is the synthesis of polymers, including nanowires and polyesters, the postcyclization of polymers, polymerization by cyclopropanation, and gold-catalyzed radical polymerization reactions. Other topics are dyes, phosphonium salts, and a wide range of extended conjugated π-systems, the latter ranging from acenes, pentalene derivatives, and different heterocyclic π-systems to fascinating applications in the synthesis of helical anellated aromatic molecules. The existing contributions clearly demonstrate the potential of gold catalysis for significant future impulses for the field of materials science.

Light-Induced Metal-Free Generation of Cyanocarbenes from Alkynyl Triazenes for the Synthesis of Nitrile Derivatives.

The chemistry of alkynyl triazenes is an emerging field for organic chemists and especially acid-induced nucleophilic functionalizations, either directly, or after a prior reaction towards aromatic triazenes under extrusion of nitrogen, paved the way for fruitful strategies. In contrast, the chemical behavior of alkynyl triazenes upon irradiation with light is still unknown. Herein we present the first photoactivation of alkynyl triazenes that triggers an uncommon reactivity pattern involving the cleavage of the N1-N2 bond of the triazene moiety resulting in a unique approach to cyanocarbenes from a readily available, stable, and insensitive precursor. This allows to access various nitrile compounds without the use of a toxic cyanating agent by exploiting the reactivity pattern of carbenes. By variation of the reaction conditions and light sources, different substitution patterns can be obtained selectively in good yields under mild and metal-free conditions, thus introducing the alkynyl triazene unit as a photo accessible methylene nitrile synthon. Using this synthon, subclasses like α-alkoxynitriles, α-aminonitriles and α-cyanohydrazones become easily available. These exhibit synthetically valuable substitution patterns for the synthesis of pharmaceuticals, intermediates for total synthesis and amino acid synthesis.

Gold-Catalyzed Formal [4+2] Cycloaddition as Access to Antitumor-Active Spirocyclic Oxindoles from Alkynes and Isatin-Derived Ketimines.

Due to its excellent bioactivity profile, which is increasingly utilized in pharmaceutical and synthetic chemistry, spirooxindole is an important core scaffold. We herein describe an efficient method for the construction of highly functionalized new spirooxindolocarbamates via a gold-catalyzed cycloaddition reaction of terminal alkynes or ynamides with isatin-derived ketimines. This protocol has a good functional group compatibility, uses readily available starting materials, mild reaction conditions, low catalyst loadings and no additives. It enables the transformation of various functionalized alkyne groups into cyclic carbamates. Gram-scale synthesis was achieved and DFT calculations verify the feasibility of the mechanistic proposal. Some of the target products exhibit good to excellent antiproliferative activity on human tumor cell lines. In addition, one of the most active compounds displayed a remarkable selectivity towards tumor cells over normal ones.

Efficient Synthesis of Dipyrrolobenzenes and Dipyrrolopyrazines via Bidirectional Gold Catalysis: a Combined Synthetic and Photophysical Study.

New N-heterocyclic fluorophores are sought-after compounds for organic electronic devices. Here, we report on a straightforward synthesis to access meta/para-dipyrrolobenzenes and para-dipyrrolopyrazines in high yields using a bidirectional gold-catalyzed cyclization strategy. The versatility of our reaction protocol was showcased by preparing dipyrroloarenes with different substituents, various functional groups, and in a multitude of substitution patterns. Furthermore, we showed that the dipyrroloarenes can be post-modified by N-alkylation to improve the solubility or bromination to yield precursors for further derivatization via cross-coupling. Investigation of the photophysical properties of the─mostly unprecedented─dipyrroloarenes identified strong blue emitters such as the diphenyl meta-dipyrrolobenzene with a quantum yield of 98%. Moreover, we showed that changes in the solvent polarity or interactions with Lewis acids such as borane can be used to fine-tune the photophysical properties of the fluorophores.

Substituted Cyclopentannulated Tetraazapentacenes.

Brominated pentannulated dihydrotetraazapentacenes were prepared by gold- or palladium-catalyzed 5-endo-dig cyclization of TIPS-ethynylated dihydrotetraazaacenes (TIPS = triisopropylsilyl). Post-functionalization was demonstrated by Sonogashira alkynylation and Rosenmund-von Braun cyanation. Calculations predict these species to act as n-type semiconductors, which was verified for two derivates through characterization in organic field-effect transistors.

Entropy-Induced Selectivity Switch in Gold Catalysis: Fast Access to Indolo[1,2-a]quinolines.

New N-heterocyclic compounds for organic functional materials and their efficient syntheses are highly demanded. A surprising entropy-induced selectivity switch in the gold-catalyzed intramolecular hydroarylation of 2-ethynyl N-aryl indoles was found and its exploitation led to straightforward syntheses of indolo[1,2-a]quinolines. Experimental and computational mechanistic investigations gave insight into this uncommon selectivity phenomenon and into the special reactivity of the indolo[1,2-a]quinolines. The high functional group tolerance of this methodology enabled access to a diverse scope with high yields. In addition, bidirectional approaches, post-functionalization reactions, and π-extension of the core structure were feasible. An in-depth study of the photophysical properties explored the structure-effect relationship for different derivatives and revealed a high potential of these compounds for future applications as functional materials.

Cyclopentannulated Dihydrotetraazapentacenes.

The transition-metal-catalyzed cyclization of bissilylethynylated N,N'-dihydrotetraazapentacene (TIPS-TAP-H2 ) into bissilylated cyclopenta[fg,qr]pentacenes is reported. Depending on the catalyst either none, one or two silyl groups migrate and change their positions in the formed five-membered rings. The optoelectronic properties are quite similar, whereas the packing motifs differ dramatically. Control experiments and quantum chemical calculations were performed to investigate the mechanism of the reaction and the selectivity of the silyl shift.

Gem-Diaurated Gold(III) Complexes: Synthesis, Structure, Aurophilic Interaction, and Catalytic Activity.

We present a protocol to synthesize air stable gem-diaurated gold(III) compounds from 1,3-diketones in a single cycloauration step with tetrachloroauric acid. So far related species were only accessible from phosphonium bis(ylide) ligands which hold the two gold atoms in close proximity. Lacking such a constraint, our compounds show the longest Au-Au distances of all gem-diaurated carbons, ranging from 3.26 to 3.32 Å. Modeling based on results of CCSD(T) calculations shows no stabilization by aurophilic interactions for our gold(III) systems, compared to 9.1 kcal/mol for gold(I) gem-diauration. This demonstrates no aurophilic interactions are needed for the isolation of air stable gem-diaurated gold(III) complexes. We show the new gem-diaurated gold(III) compounds are active in the gold-catalyzed phenol synthesis and highly active in the cycloisomerization of an N-propargylcarboxamide; here, we obtained the so far highest known TON of over 2500 per gold atom with respect to the oxazole formation.

Modular Two-Step Access to π-Extended Naphthyridine Systems-Potent Building Blocks for Organic Electronics.

Efficient synthetic approaches for the incorporation of nitrogen into polyaromatic compounds (PACs) in different patterns as stabilising moiety for π-extended systems and modification tool for optoelectronic properties remain a challenge until today. Herein, we developed a new versatile pathway to napthyridine-based PACs as non-symmetric and regioisomeric pendant to pyrazine-based PACs. A combination of a gold-catalysed synthesis of 2-aminoquinolines and the development of an in situ desulfonation and condensation of these precursors are the key steps of the protocol. The shape and type of attached functional groups of the PACs can be designed in a late stage of the overall synthetic procedure by the chosen anthranile and backbone of the ynamide introduced in the gold-catalysed step. Single-crystal X-ray diffraction and the investigation of electronic properties of the compounds show the influence of the attached substituents. All naphthyridine-based PACs show halochromic behaviour implying their use as highly sensitive proton sensor in non-protic solvents.